1.Joint Relation Extraction of Famous Medical Cases with CasRel Model Combining Entity Mapping and Data Augmentation
Yuxin LI ; Xinghua XIANG ; Hang YANG ; Dasheng LIU ; Jiaheng WANG ; Zhiwei ZHAO ; Jiaxu HAN ; Mengjie WU ; Qianzi CHE ; Wei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):218-225
ObjectiveTo address the challenges of unstructured classical Chinese expressions, nested entity relationships, and limited annotated data in famous traditional Chinese medicine(TCM) case records, this study proposes a joint relation extraction framework that integrates data augmentation and entity mapping, aiming to support the construction of TCM diagnostic knowledge graphs and clinical pattern mining. MethodsWe developed an annotation structure for entities and their relationships in TCM case texts and applied a data augmentation strategy by incorporating multiple ancient texts to expand the relation extraction dataset. A cascade binary tagging framework for relation triple extraction(CasRel) model for TCM semantics was designed, integrating a pre-trained bidirectional encoder representations from transformers(BERT) layer for classical TCM texts to enhance semantic representation, and using a head entity-relation-tail entity mapping mechanism to address entity nesting and relation overlapping issues. ResultsExperimental results showed that the CasRel model, combining data augmentation and entity mapping, outperformed the pipeline-based Bert-Radical-Lexicon(BRL)-bidirectional long short-term memory(BiLSTM)-Attention model. The overall precision, recall, and F1-score across 12 relation types reached 65.73%, 64.03%, and 64.87%, which represent improvements of 14.26%, 7.98%, and 11.21% compared to the BRL-BiLSTM-Attention model, respectively. Notably, the F1-score for tongue syndrome relations increased by 22.68%(69.32%), and the prescription-syndrome relations performed the best with the F1-score of 70.10%. ConclusionThe proposed framework significantly improves the semantic representation and complex dependencies in TCM texts, offering a reusable technical framework for structured mining of TCM case records. The constructed knowledge graph can support clinical syndrome differentiation, prescription optimization, and drug compatibility, providing a methodological reference for TCM artificial intelligence research.
2.Effect of Qingfei Shenshi Decoction (清肺渗湿汤) Combined with Western Medicine on Clinical Effectiveness and Immune Function for Patients with Bronchial Asthma of Heat Wheezing Syndrome
Ying SUN ; Haibo HU ; Na LIU ; Fengchan WANG ; Jinbao ZONG ; Ping HAN ; Peng LI ; Guojing ZHAO ; Haoran WANG ; Xuechao LU
Journal of Traditional Chinese Medicine 2026;67(1):38-44
ObjectiveTo observe the clinical effectiveness and safety of Qingfei Shenshi Decoction (清肺渗湿汤) combined with western medicine for patients with bronchial asthma of heat wheezing syndrome, and to explore its potential mechanism of action. MethodsEighty-six participants with bronchial asthma of heat wheezing syndrome were randomly divided into treatment group and control group, each group with 43 participants. The control group received conventional western medicine, and the treatment group was additionally administered Qingfei Shenshi Decoction orally on the basis of the control group, 1 dose per day. Both groups were treated for 14 days. The primary outcome measure was clinical effectiveness; secondary outcome measures included traditional Chinese medicine (TCM) syndrome score, asthma control test (ACT) score, pulmonary function indices such as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), serum inflammatory factor levels including interleukin-4 (IL-4), tumour necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP), and immune function indices including CD3+, CD4+, CD8+, CD4+/CD8+. All outcome measures were evaluated before and after treatment. Vital signs were monitored, and electrocardiography, blood routine, urine routine, liver function, and renal function tests were performed before and after treatment. Adverse events and reactions during the study were recorded. ResultsA total of 80 patients completed the trial with 40 in each group. The total clinical effective rate of the treatment group was 97.5% (39/40), which was significantly higher than that of the control group (85.0%, 34/40, P<0.05). After treatment, both groups showed decreased TCM syndrome scores, IL-4, TNF-α, hs-CRP, and CD8+ levels, as well as increased ACT scores, CD3+, CD4+, CD4+/CD8+, FEV1, FVC, and PEF levels (P<0.05 or P<0.01). Moreover, the improvements in these indices were more significant in the treatment group than in the control group (P<0.05 or P<0.01). No significant abnormalities in safety indicators were observed in either group, and no adverse events or reactions occurred. ConclusionQingfei Shenshi Decoction combined with conventional western medicine for patients with bronchial asthma of heat wheezing syndrome can effectively improve the clinical symptoms, pulmonary function, and clinical effectiveness, with good safety. Its mechanism may be related to reducing inflammatory factor levels and regulating T lymphocyte subsets to improve immune function.
3.Treatment Principles and Paradigm of Diabetic Microvascular Complications Responding Specifically to Traditional Chinese Medicine
Anzhu WANG ; Xing HANG ; Lili ZHANG ; Xiaorong ZHU ; Dantao PENG ; Ying FAN ; Min ZHANG ; Wenliang LYU ; Guoliang ZHANG ; Xiai WU ; Jia MI ; Jiaxing TIAN ; Wei ZHANG ; Han WANG ; Yuan XU ; .LI PINGPING ; Zhenyu WANG ; Ying ZHANG ; Dongmei SUN ; Yi HE ; Mei MO ; Xiaoxiao ZHANG ; Linhua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):272-279
To explore the advantages of traditional Chinese medicine (TCM) and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications (DMC), refine key pathophysiological insights and treatment principles, and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine, hosted by the China Association of Chinese Medicine, was held in Beijing, 2024. Experts in TCM, Western medicine, and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis, diagnostic and treatment challenges, and mechanism research related to DMC, ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development, research prioritization, and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM, strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.
4.Effects of bioactive peptides combined with probiotics on serum uric acid in patients with hyperuricemia
HAN Dan ; ZHAO Ya ; HUANG Enshan ; YE Shuhua ; WANG Wanjin ; WU Fangmin ; WANG Dingliang ; ZHANG Ronghua
Journal of Preventive Medicine 2025;37(1):40-45
Objective:
To evaluate the effect of bioactive peptides combined with probiotics on serum uric acid (SUA) in patients with hyperuricemia (HUA), so as to provide the evidence for prevention and treatment of HUA.
Methods:
The patients with HUA aged 18 to 65 years were selected and randomly divided into an intervention group and a control group. The patients in the intervention group received bioactive peptides combined with probiotics for 28 days at a dose of 3 g/d, while the patients in the control group received an equal dose of placebos. Demographic information, body mass index (BMI), blood pressure and blood lipid were collected through questionnaire surveys, physical examination and laboratory tests. SUA levels were detected before and after 14 days and 28 days of interventions. The differences of SUA levels between the two groups were compared using generalized estimation equation.
Results:
Totally 108 patients with HUA were recruited, including 54 patients in the intervention group and 53 patients in the control group (1 dropout). Before interventions, there were no statistically significant differences in gender, age, course of HUA, exercise duration, frequency of alcohol consumption, frequency of meat broth consumption, BMI, prevalence of hypertension and prevalence of dyslipidemia between the two groups (all P>0.05). After 14 days of interventions, the SUA levels of the patients in the intervention group decreased by 3.00 μmol/L, while those in the control group increased by 7.00 μmol/L. After 28 days of interventions, the SUA levels of the patients in the intervention group and the control group decreased by 26.00 μmol/L and 16.00 μmol/L, respectively. However, there was no statistically significant interaction between the intervention time and group (both P>0.05). Subgroup analysis showed that after 28 days of interventions, the decrease in SUA levels in the patients aged 55 years and older and without hypertension in the intervention group was greater than those in the control group (both P<0.05).
Conclusions
Bioactive peptides combined with probiotics showed no significant difference in reducing SUA levels in patients with HUA compared to the control group. The effect was more significant for patients aged 55 years and older and without hypertension.
5.Construction and Application Evaluation of an Integrated Traditional Chinese and Western Medicine Risk Prediction Model for Readmission in Patients with Stable Angina of Coronary Heart Disease:A Prospective Study Based on Real-World Clinical Data
Wenjie HAN ; Mingjun ZHU ; Xinlu WANG ; Rui YU ; Guangcao PENG ; Qifei ZHAO ; Jianru WANG ; Shanshan NIE ; Yongxia WANG ; Jingjing WEI
Journal of Traditional Chinese Medicine 2025;66(6):604-611
ObjectiveBy exploring the influencing factors of readmission in patients with stable angina of coronary heart disease (CHD) based on real-world clinical data, to establish a risk prediction model of integrated traditional Chinese and western medicine, in order to provide a basis for early identification of high-risk populations and reducing readmission rates. MethodsA prospective clinical study was conducted involving patients with stable angina pectoris of CHD, who were divided into a training set and a validation set at a 7∶3 ratio. General information, traditional Chinese medicine (TCM)-related data, and laboratory test results were uniformly collected. After a one-year follow-up, patients were classified into a readmission group and a non-readmission group based on whether they were readmitted. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for readmission. A risk prediction model of integrated traditional Chinese and western medicine was constructed and visualized using a nomogram. The model was validated and evaluated in terms of discrimination, calibration, and clinical decision curve analysis. ResultsA total of 682 patients were included, with 477 in the training set and 205 in the validation set, among whom 89 patients were readmitted. Multivariate logistic regression analysis identified heart failure history [OR = 6.93, 95% CI (1.58, 30.45)], wiry pulse [OR = 2.58, 95% CI (1.42, 4.72)], weak pulse [OR = 3.97, 95% CI (2.06, 7.67)], teeth-marked tongue [OR = 4.38, 95% CI (2.32, 8.27)], blood stasis constitution [OR = 2.17, 95% CI (1.06, 4.44)], phlegm-stasis mutual syndrome [OR = 3.64, 95% CI (1.87, 7.09)], and elevated non-high-density lipoprotein cholesterol [OR = 1.30, 95% CI (1.01, 1.69)] as influencing factors of readmission. These factors were used as predictors to construct a nomogram-based risk prediction model for readmission in patients with stable angina. The model demonstrated moderate predictive capability, with an area under the receiver operating characteristic curve (AUC) of 0.818 [95% CI (0.781, 0.852)] in the training set and 0.816 [95% CI (0.779, 0.850)] in the validation set. The Hosmer-Lemeshow test showed good calibration (χ² = 4.55, P = 0.80), and the model's predictive ability was stable. When the threshold probability exceeded 5%, the clinical net benefit of using the model to predict readmission risk was significantly higher than intervening in all patients. ConclusionHistory of heart failure, teeth-marked tongue, weak pulse, wiry pulse, phlegm-stasis mutual syndrome, blood stasis constitution, and non-high-density lipoprotein cholesterol are influencing factors for readmission in patients with stable angina of CHD. A clinical prediction model was developed based on these factors, which showed good discrimination, calibration, and clinical utility, providing a scientific basis for predicting readmission events in patients with stable angina.
6.Intelligent handheld ultrasound improving the ability of non-expert general practitioners in carotid examinations for community populations: a prospective and parallel controlled trial
Pei SUN ; Hong HAN ; Yi-Kang SUN ; Xi WANG ; Xiao-Chuan LIU ; Bo-Yang ZHOU ; Li-Fan WANG ; Ya-Qin ZHANG ; Zhi-Gang PAN ; Bei-Jian HUANG ; Hui-Xiong XU ; Chong-Ke ZHAO
Ultrasonography 2025;44(2):112-123
Purpose:
The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations.
Methods:
This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits.
Results:
Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01).
Conclusion
Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.
7.Synthetic MRI Combined With Clinicopathological Characteristics for Pretreatment Prediction of Chemoradiotherapy Response in Advanced Nasopharyngeal Carcinoma
Siyu CHEN ; Jiankun DAI ; Jing ZHAO ; Shuang HAN ; Xiaojun ZHANG ; Jun CHANG ; Donghui JIANG ; Heng ZHANG ; Peng WANG ; Shudong HU
Korean Journal of Radiology 2025;26(2):135-145
Objective:
To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC).
Materials and Methods:
Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test.
Results:
The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively.
Conclusion
SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.
8.Value of third lumbar skeletal muscle mass index in predicting the prognosis of patients with acute-on-chronic liver failure
Yewen HAN ; Jing LI ; Ninghui ZHAO ; Jia YAO ; Juan WANG
Journal of Clinical Hepatology 2025;41(4):698-702
ObjectiveTo investigate the value of third lumbar skeletal muscle mass index (L3-SMI) in predicting the long-term prognosis of patients with acute-on-chronic liver failure (ACLF), and to provide a useful tool for prognostic scoring of ACLF patients. MethodsA retrospective analysis was performed for the data of 126 patients who underwent abdominal computed tomography (CT) scanning and were diagnosed with ACLF in Shanxi Bethune Hospital from December 2017 to December 2021, including clinical indicators, biochemical parameters, and model for end-stage liver disease (MELD) score, and L3-SMI was calculated. The independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic (ROC) curve was used to assess the diagnostic value of L3-SMI and other variables (MELD score and Child-Pugh score), and the DeLong test was used for comparison of the area under the ROC curve (AUC). ResultsAmong the 126 patients enrolled, 44 (35%) died within 2 years and 82 (65%) survived. Compared with the survival group, the death group had significantly higher age, incidence rate of ascites, international normalized ratio, MELD score, and Child-Pugh score (all P<0.05) and a significantly lower value of L3-SMI [38.40 (35.95 — 46.29) cm²/m² vs 44.19 (40.20 — 48.58) cm²/m², Z=-2.855, P=0.004]. L3-SMI had an AUC of 0.720 in predicting 2-year mortality in ACLF patients, with a sensitivity of 63.6% and a specificity of 80.5%, and a combination of L3-SMI, MELD score, and Child-Pugh score had a significantly better AUC than a combination of MELD score and Child-Pugh score in predicting 2-year mortality (0.809 vs 0.757, Z=2.015, P<0.05). ConclusionL3-SMI has a high predictive value for the prognosis of ACLF patients, and the combination of L3-SMI、MELD score and Child-Pugh score has a higher predictive value for ACLF patients, and the inclusion of L3-SMI or sarcopenia in the conventional prognostic scores of ACLF patients may increase the ability to predict disease progression.
9.Effect of Linggui Zhugantang on Ventricular Remodeling After Myocardial Infarction and RhoA/ROCK Signaling Pathway
Han REN ; Wanzhu ZHAO ; Shushu WANG ; Rui CAI ; Yuanhong ZHANG ; Shengyi HUANG ; Jinling HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):1-9
ObjectiveThis study aims to investigate the effects of Linggui Zhugantang (LGZGT) on ventricular remodeling (VR) in mice with myocardial infarction (MI) and its impact on the Ras homologgene A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway. MethodsThe MI model of mice was established by ligating the left anterior descending coronary artery (LAD). They were divided into the sham-operated group, the model group, the low-dose, medium-dose, and high-dose groups of LGZGT (2.34, 4.68, 9.36 g·kg-1), and the captopril group (3.25 mg·kg-1), with 10 mice in each group. After four weeks of continuous drug administration by gavage, the level of cardiac function in each group of mice was examined using small animal Doppler ultrasound. Hematoxylin-eosin (HE) staining and Masson staining was used to assess the morphological changes of myocardial tissue and calculate the rate of collagen fiber deposition in mouse myocardial tissue. Wheat germ agglutinin (WGA) staining was employed to compare the cross-sectional area of cardiomyocytes in each group of mice. The expression levels of α-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), type Ⅰcollagen (Col Ⅰ), Col Ⅲ, tissue inhibitor of metalloproteinase 1(TIMP1), B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), Bcl-2, Caspase-3, and cleaved Caspase-3 were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to evaluate the mRNA levels of the pathway-related genes RhoA, ROCK1, and ROCK2. The protein expression levels of RhoA, ROCK1, and ROCK2 were tested by Western blot. ResultsThe level of cardiac function was markedly declined in the model group compared to the sham-operated group(P<0.01). Myocardial tissue morphology changed significantly. The cross-sectional area of cardiomyocytes was significantly enlarged. The expression of α-SMA, MMP-2, Col Ⅰ, and Col Ⅲ was significantly upregulated(P<0.01), and TIMP1 protein expression was significantly reduced(P<0.01). The expressions of apoptosis-related proteins Bax were significantly up-regulated(P<0.01), while the expression of Bcl-2 protein was significantly decreased(P<0.01). The mRNA expression of RhoA, ROCK1, and ROCK2 were significantly upregulated (P<0.01). Compared to the model group, the low-dose, medium-dose, and high-dose groups of LGZGT and the captopril group significantly reversed the experimental results of the model group in a dose-dependent manner (P<0.05, P<0.01). ConclusionLGZGT significantly attenuated myocardial fibrosis, myocardial hypertrophy, and cardiomyocyte apoptosis after MI in mice and effectively reversed VR, the mechanism of which may be related to the modulation of the RhoA/ROCK signaling pathway.
10.Effect of Linggui Zhugantang on Ventricular Remodeling After Myocardial Infarction and RhoA/ROCK Signaling Pathway
Han REN ; Wanzhu ZHAO ; Shushu WANG ; Rui CAI ; Yuanhong ZHANG ; Shengyi HUANG ; Jinling HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):1-9
ObjectiveThis study aims to investigate the effects of Linggui Zhugantang (LGZGT) on ventricular remodeling (VR) in mice with myocardial infarction (MI) and its impact on the Ras homologgene A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway. MethodsThe MI model of mice was established by ligating the left anterior descending coronary artery (LAD). They were divided into the sham-operated group, the model group, the low-dose, medium-dose, and high-dose groups of LGZGT (2.34, 4.68, 9.36 g·kg-1), and the captopril group (3.25 mg·kg-1), with 10 mice in each group. After four weeks of continuous drug administration by gavage, the level of cardiac function in each group of mice was examined using small animal Doppler ultrasound. Hematoxylin-eosin (HE) staining and Masson staining was used to assess the morphological changes of myocardial tissue and calculate the rate of collagen fiber deposition in mouse myocardial tissue. Wheat germ agglutinin (WGA) staining was employed to compare the cross-sectional area of cardiomyocytes in each group of mice. The expression levels of α-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), type Ⅰcollagen (Col Ⅰ), Col Ⅲ, tissue inhibitor of metalloproteinase 1(TIMP1), B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), Bcl-2, Caspase-3, and cleaved Caspase-3 were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to evaluate the mRNA levels of the pathway-related genes RhoA, ROCK1, and ROCK2. The protein expression levels of RhoA, ROCK1, and ROCK2 were tested by Western blot. ResultsThe level of cardiac function was markedly declined in the model group compared to the sham-operated group(P<0.01). Myocardial tissue morphology changed significantly. The cross-sectional area of cardiomyocytes was significantly enlarged. The expression of α-SMA, MMP-2, Col Ⅰ, and Col Ⅲ was significantly upregulated(P<0.01), and TIMP1 protein expression was significantly reduced(P<0.01). The expressions of apoptosis-related proteins Bax were significantly up-regulated(P<0.01), while the expression of Bcl-2 protein was significantly decreased(P<0.01). The mRNA expression of RhoA, ROCK1, and ROCK2 were significantly upregulated (P<0.01). Compared to the model group, the low-dose, medium-dose, and high-dose groups of LGZGT and the captopril group significantly reversed the experimental results of the model group in a dose-dependent manner (P<0.05, P<0.01). ConclusionLGZGT significantly attenuated myocardial fibrosis, myocardial hypertrophy, and cardiomyocyte apoptosis after MI in mice and effectively reversed VR, the mechanism of which may be related to the modulation of the RhoA/ROCK signaling pathway.


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